Gene encoding organic anion transporter

Abstract

This invention is concerned with human organic anion transporter (“hOAT”). Isolated nucleic acid encoding hOAT is provided, along with isolated hOAT polypeptide. hOAT nucleic acid and/or hOAT polypeptide are employed in transgenic animals, recombinant cells, replicable vectors and analytical procedures for identifying hOAT agonists or antagonists, assays for identifying hOAT alleles and/or isotypes, screening tests for nephrotoxic or neurologically active compounds, and determination of drug-drug interactions within the kidney or brain.

What is claimed is:  
     
       1. A method for identifying an inhibitor of the hOAT mediated transport process comprising (a) providing a recombinant cell culture expressing biologically active hOAT having the amino acid sequence of SEQ ID No. 2, and providing a covalently modified form of a nucleotide phosphonate analogue a candidate inhibitor and (b) determining whether or not the analogue is transported by hOAT in the recombinant cell culture. 
     
     
       2. The method of  claim 1  wherein the nucleotide phosphonate analogue is a derivative of PMEA, cidofovir or PMPA. 
     
     
       3. The method of  claim 1  wherein the recombinant cell is a eukaryotic cell. 
     
     
       4. A method for identifying a drug-drug interaction comprising contacting a candidate drug with (a) a recombinant cell culture expressing hOAT polypeptide having SEQ ID No. 2 and (b) at least a second drug whose effect on hOAT-medicated transport in said cell culture of the candidate drug is to be determined, and analyzing the effect of the second one or more drugs on hOAT-mediated transport in said cell culture of the candidate drug. 
     
     
       5. The method of  claim 4  wherein the recombinant cell is a eukaryotic cell.